Nutritional and anaemia status of children with Downs syndrome - A tertiary care experience

Down syndrome (DS) is the most common genetic cause of intellectual disability, yet the cellular and molecular mechanisms driving this developmental disorder remain unclear. In this study, we profiled human mid-gestation neocortex with snMultiomics across 26 donors. We observed a reduction in neural progenitors and corticothalamic neurons and an increase of intratelencephalic neurons, accompanied by accelerated neuronal specification. We uncovered widespread changes in gene expression, chromatin accessibility, and cell interaction networks affecting neurogenesis, specification, and maturation; and in gene-regulatory networks directing these processes, including those downstream of human chromosome 21 (HSA21)-encoded genes. We identified cell-specific molecular pathways shared with other neurodevelopmental disorders and enrichment of genome-wide association study signals in DS-altered chromatin. Together, our data revealed a cascade of molecular dysregulation outlining the earliest steps in DS, providing a foundation for future therapeutic targets.

Background/Objectives: Down syndrome (DS) is characterised by a marked susceptibility to early-onset severe periodontitis, suggesting an intrinsic host predisposition. Interleukin-1 (IL-1) gene variants may influence inflammatory burden, yet DS-specific evidence is limited. Methods: Nineteen Caucasian adults with DS underwent a comprehensive periodontal examination and received a periodontal diagnosis according to the AAP/EFP 2018 classification. Buccal swabs were genotyped by real-time PCR for IL1A −889, IL1B +3954 and IL1RN +2018; the composite IL1A/B genotype was also evaluated. Results: All participants presented advanced, generalized periodontitis (Stage III/IV: 37%/63%; Grade B/C: 32%/68%). Variant alleles were detected in 63% for IL1A, 53% for IL1B and 37% for IL1RN, and the composite IL-1A/B genotype in 47%. Variant carriage showed associations with higher Clinical Attachment Loss (IL1A p = 0.03; IL1B p = 0.002; composite p = 0.012) and Bleeding on Probing (IL1A p = 0.02; IL1RN p = 0.05; composite p = 0.04). The composite genotype was associated with Stage IV (p = 0.027) and Grade C (p = 0.005), and tooth loss was greater among variant carriers for all polymorphisms (p = 0.01). Conclusions: In this DS cohort with advanced periodontitis, IL-1 variants (particularly the composite IL1A/B genotype) were frequently observed and were associated with greater periodontal severity and tooth loss.

ABSTRACT Unquestionably, with the increase in life expectancy, dementia has become a significant health issue in Down syndrome (DS). However, in at least a subset of these individuals, cognitive aging can be considered normal, with absence of dementia symptoms even in the presence of Alzheimer's neuropathology. Therefore, it is essential to understand the complex interactions between risk and protective factors for dementia in this population. Studies are needed to address and elucidate those factors that may improve resilience against cognitive deterioration. Cognitive reserve (CR) is a theoretical construct proposed to explain variability in responses despite similar brain insults. Research addressing CR proxies in people with intellectual disability is limited; evidence is mostly derived from literature reviews or extrapolations from other populations. The present study aims to explore the association between specific proxies of CR and the occurrence of cognitive decline and dementia among adults with DS. Two complementary methodologies were adopted: a retrospective and observational study and a cross‐sectional study involving aging adults with DS. Severe levels of intellectual disability and older age were associated with a higher prevalence of cognitive decline or dementia. We observed a correlation between some proxies of CR. Previous engagement in occupational activities was correlated with regular school attendance, and higher parental education was associated with increased literacy in individuals with Down syndrome. The level of intellectual disability was associated with cognitive decline. Previous engagement in occupational activities and regular school attendance were identified as factors that may be associated with the construct of cognitive reserve and deserve future investigation. Higher parental education was a potential parameter that appears to affect the literacy of their child with trisomy 21.

This study examined the association between sensory-rich messy play and language development in children with Down syndrome (DS) and children with intellectual disabilities of unknown etiology (IDUE). Drawing on Vygotsky’s sociocultural theory and the framework of embodied cognition, the study investigated whether different play contexts are differentially associated with expressive and receptive language outcomes across developmental populations. A 2 × 2 quasi-experimental pretest–posttest design was employed. Forty children aged 4 to 6 years were assigned to one of four conditions based on diagnostic group (DS vs. IDUE) and intervention type (sensory-rich messy play vs. structured non-sensory play). Language development was assessed before and after a 12-week intervention using the LaTo standardized test. Mixed-design analyses of variance revealed significant improvements in language performance over time, as well as significant effects of intervention type and diagnostic group. Children who participated in sensory-rich messy play demonstrated greater gains in expressive and receptive language compared to those engaged in structured play. A significant interaction between diagnostic group and intervention type was also observed, indicating that the association between play context and language development differed across groups. In particular, children with DS in the messy play condition showed the most pronounced improvements, especially in expressive language. These findings suggest that sensory-rich play contexts are associated with enhanced language outcomes, particularly for children with DS. However, due to the quasi-experimental design, causal interpretations should be made with caution. These findings suggest that sensory-rich play contexts are associated with enhanced short-term language outcomes, particularly for children with DS. However, due to the quasi-experimental design and the absence of follow-up assessment, conclusions regarding long-term or causal effects should be made with caution.

ABSTRACT Down syndrome (DS) is a common genetic condition, and non-pharmacological interventions are increasingly utilized to address associated developmental and health-related challenges. Among these, animal-assisted interventions (AAIs) have gained recognition for their therapeutic potential across various populations; however, a focused synthesis of their application within the DS population has been lacking. This scoping review aimed to characterize the key features of AAIs and to document the methodological characteristics of existing research involving individuals with DS. A systematic search of five databases (PubMed, PsycINFO, EMBASE, CINAHL, and Scopus) was conducted in August 2024, yielding 27 eligible peer-reviewed articles. The findings revealed that most studies involved children and adolescents, with limited inclusion of adult participants. Methodological diversity was not seen, including a lack of randomized controlled trials, longitudinal designs, and incorporation of caregiver or participant perspectives. Additionally, there was considerable variability in intervention parameters and a lack of standardized, evidence-based guidelines for implementation. These findings underscore the need to broaden methodological approaches and incorporate a lifespan perspective to better inform best practices in the use of AAIs for individuals with Down syndrome.

Past research on interactions between parents and their children with Down syndrome (DS) has focused on mothers as the communication partner, despite fathers also frequently interacting with their children. This exploratory study examined mother and father question-asking behaviors during dyadic interactions with their children with DS and included preliminary observations of children's responsiveness to capture the bidirectional nature of interaction. Participants included 15 children with DS (Mage = 39.67 months) and their biological parents. Each participant was administered the Mullen Scales of Early Learning. Ten-minute interactions for mother-child and father-child dyads were video-recorded during free-play in their home. Analyses examined the differences in the rate and type of questions between mothers and fathers and whether question asking was associated with children's nonverbal developmental quotient (NVDQ), language ability, chronological age, or rate of response. Mothers asked significantly more questions than fathers, including more open-ended, closed-ended, and rhetorical questions, as well as specific subtypes of closed-ended questions. Within individual family units, mothers asked more questions than fathers in 10 of the 15 families studied. Exploratory observations of child responses suggested that responsiveness varied across dyads. Parental questioning behaviors were associated with children's NVDQs and chronological age, but not language ability. Results underscore the importance of including both parents in language interventions for children with DS and suggest that parents naturally adjust their questioning strategies based on children's NVDQs and chronological age rather than language skills. https://doi.org/10.23641/asha.31842937.

Down syndrome (DS) is one of the most common developmental human genetic disorders and is due to triplication of chromosome 21 (HSA21). Although previous studies using epigenetic suppression of HSA21 by the long noncoding RNA XIST showed a potential for DS treatment, integration efficiency of XIST by conventional zinc finger nucleases is too low to allow for practical implementation. Here, we report a modified CRISPR/Cas9 approach, which enhances the efficiency of XIST gene integration. First, a codon-optimized λ-phage exonuclease (exo) was fused with Cas9 to create 5'- and 3'-end overhangs at cutting sites of donor DNA and acceptor chromosome DNA. Second, four sgRNAs, two of which selectively targeted each the acceptor or donor DNA, were assembled tandemly into one Cas9 plasmid (PX459) to increase the Cas9-cutting efficiency and promote donor DNA integration. Third, sgRNAs were designed by searching for unique single nucleotide polymorphism nucleotides distinct between the three HSA21 copies, as a protospacer adjacent motif site to specifically target one HSA21 copy. Fourth, donor DNA plasmid containing XIST was modified to disable replication and inhibit transcription function and allow for inducible expression. Our modified CRISPR method significantly enhanced the integration efficiency (20 to 40%) of long XIST gene (14 kb) into an extra chromosome 21 (HSA21), as was identified with PCR, cell cloning, immunostaining, and FISH. RNA sequencing results showed that imbalance of gene transcription across extra HSA21 can be partially corrected by XIST gene integration. The modified CRISPR method with XIST paves a road for therapeutic treatment for DS.

Partial trisomy 21 is a rare chromosomal aberration that can provide unique insights into genotype-phenotype correlations in Down syndrome (DS). While non-invasive prenatal testing (NIPT) has become a widely used screening tool for common aneuploidies, its sensitivity is limited in cases of low-level mosaicism or partial duplications. We report a de novo partial trisomy 21 encompassing the entire Down syndrome critical region (DSCR) that escaped NIPT. A 38-year-old first gravida underwent NIPT for evaluation of fetal trisomies 13, 18 or 21 as well as monosomy X, which showed normal results. Ultrasound at 19 + 5 weeks of gestation revealed polyhydramnios and a left-sided fetal hydrothorax, prompting amniocentesis. By karyotyping, a derivative chromosome 21 carrying additional material on the p-arm was identified. PCR-based microsatellite analysis, FISH and array-based studies on amniotic cells characterized the attached material as a de novo terminal duplication of 11.8Mb of chromosome 21q22.12q22.3, fully encompassing the DSCR and without evidence of mosaicism. Comprehensive genetic counselling was provided, and the pregnancy was electively terminated at 24 weeks of gestation. Postmortem examination of the fetus revealed phenotypic features consistent with Down syndrome. In contrast to the non-mosaic duplication observed in amniotic fluid cells, post-termination tissue analysis demonstrated placental mosaicism, comprising predominantly a normal male cell line and a chromosomal aberrant male cell line with partial duplication of 21q22.12q22.3 in 28% of interphase nuclei in short-term cultured chorionic villi. This constellation likely explains the normal NIPT result. This case illustrates the limitations of NIPT in detecting partial trisomies and low-grade placental mosaicism. It emphasizes the importance of further invasive prenatal investigations when results of ultrasound and NIPT are discrepant and it contributes to the understanding of genotype-phenotype correlations in partial trisomy 21. Clinicians should be aware that partial duplications of 21q22 can produce a full DS phenotype despite unremarkable NIPT results. This case highlights the challenges of technical choices in prenatal diagnostics and emphasizes the need for careful interpretation of screening tests and targeted counselling.

Down syndrome (DS) is a widespread chromosomal disorder primarily associated with cognitive impairment and progressive neurodegenerative changes. Clinically, age 50 years is considered a pivotal turning point in the health trajectory of individuals with DS. Before this age, they primarily face developmental challenges including significant cognitive deficits and difficulties in social interaction. However, as they age, they increasingly exhibit more severe neurodegenerative changes, including Alzheimer's disease (AD)-like cognitive decline and dementia symptoms. This study aimed to dissect intricate gene expression patterns in key neuronal cell types within the DS cerebral cortex and to examine how these patterns evolve with age.We conducted a detailed gene expression analysis of key neuronal cells, including inhibitory neurons, excitatory neurons, microglia, and oligodendrocyte progenitor cells, in individuals with DS. Additionally, the bioinformatics tool NeuronChat was employed to investigate the intercellular communication networks in the DS brain.Individuals with DS were divided into younger and older groups, with age 50 years as the boundary. Through comparative analysis, our findings indicated that aging in DS is associated with exacerbated neuronal dysfunction, decreased energy metabolism in microglia, and increased neurodegenerative traits in oligodendrocyte progenitor cells. Notably, compared to the control group, the DS brain showed increased complexity in cellular communication networks, reflecting an effort to maintain adaptability during syndrome progression. However, this increased complexity does not translate into effective signal transmission, suggesting significant disruptions in the function and structure of the neural network.This study provides a deeper understanding of cell function abnormalities and signal transmission irregularities in DS. By integrating single-cell and systemic network analyses, we revealed complex pathophysiological mechanisms, laying a foundational framework for developing new treatment methods. Our comprehensive analysis emphasizes the necessity for targeted strategies to address the multifaceted nature of DS pathogenesis and improve treatment outcomes.

Polycomb repressive complex 2 insufficiency underlies myeloid leukemia in Down syndrome.

BackgroundThe World health organization (WHO) identifies Down syndrome (DS) as one among common congenital disorders, along with congenital heart defects. Approximately fifty percent of children diagnosed with DS are affected by congenital heart defects which significantly impact their survival. Nevertheless, in low and middle income countries, there is limited published data on congenital heart defects in children with DS and their treatment outcomes. Therefore, this study aimed to document the clinical characteristics and hospital outcomes of children with DS who were diagnosed with heart defects. The goal is to assist healthcare providers and policymakers in improving care for these children.MethodsThis was a retrospective descriptive study of children with DS diagnosed with heart disease admitted at the Jakaya Kikwete Cardiac Institute (JKCI) from December 2022 through December 2024. Socio-demographics, clinical characteristics, and survival data were extracted from medical records. Frequencies and proportions were calculated for categorical variables. The description of mean with standard deviation (SD) and median with and interquartile range (IQR) were calculated for continuous data. For the missing data, the case deletion approach was used.ResultsIn two years, out of 1,356 admitted children, data from 104 children with Down syndrome were analysed. Most of them, 93.2%, were aged below 5 years, with a slight predominance of male children, of almost 58%. Fifty percent (58/104) of study participants resided in the coastal region of Tanzania, followed by the northern zone (19.2%, 20/104). The most frequent cardiac diagnoses were AVSD, 46.2% and VSD, 14.4% with a median age at diagnosis of 5 months (IQR, 3.3–10). The median age of the mothers was 38 years (IQR, 38–42) while the mean age of the fathers was 36.9 years (SD, ± 7.1). At discharge, nearly a quarter, 19.2% of children had prolonged hospital stays of more than 2 weeks, and 7.7% (8/104) of enrolled children died. Nevertheless, 4.8% of children with Down syndrome underwent open cardiac surgery during the study period.ConclusionAdvanced maternal age, paternal age and AVSD were frequently observed in this study, nevertheless; a significant number of the enrolled children were first diagnosed beyond 5 months of age. Hence, the study recommends early screening echocardiography among children with Down syndrome and more studies with a large sample size to evaluate long-term outcomes in this population.

Application of machine learning to blood‐based biomarkers of Alzheimer's disease in Down syndrome

ABSTRACTIndividuals with Down syndrome (DS) are at risk for early‐onset Alzheimer's disease (AD), marked by neurodegeneration in hippocampal and basal forebrain circuits. Early‐life interventions offer therapeutic potential, including maternal choline supplementation (MCS). MCS improves cognitive outcomes and neuroplasticity in rodent models of neurodevelopmental and neurodegenerative disorders, yet cell‐type specific molecular effects remain unknown. We investigated the effect of MCS upon the onset of septohippocampal degeneration at 6 months of age in the Ts65Dn mouse model of DS/AD. Using laser capture microdissection and single population RNA‐sequencing, transcriptomic changes were profiled within hippocampal CA1 and CA3 pyramidal neurons and dentate gyrus granule cells comparing trisomic and disomic offspring. Bioinformatic analysis revealed MCS‐mediated downregulation of apoptotic pathways and upregulation of cognition‐related functions across all populations, alongside cell‐specific responses. These findings highlight MCS as a promising strategy for modulating disease‐relevant pathways in a hippocampal cell‐type–specific manner during early neurodegeneration in DS/AD.

This review explores Alzheimer's disease (AD) in individuals with Down syndrome (DS), a genetically defined population with near-universal development of AD neuropathology by age 40. We examine the genetic basis of DS-AD, epidemiology, biomarker trajectories, and clinical trial innovations, highlighting how insights from DS research inform broader AD pathogenesis, early detection, and therapeutic strategies. Advances in biomarker research, including longitudinal studies such as ABC-DS, have mapped predictable trajectories of amyloid, tau, and neurodegeneration in DS-AD, aligning closely with clinical staging. Plasma and CSF biomarkers (Aβ42, p-tau, NfL, GFAP) and neuroimaging modalities (amyloid/tau PET, MRI) demonstrate early and sequential changes decades before dementia onset. Revised AD diagnostic criteria now classify DS individuals as Stage 0 from birth, acknowledging genetic determinism and enabling earlier intervention. Comparative analyses between DS-AD, autosomal-dominant AD, and sporadic AD reveal shared pathological features but distinct timing and distribution of amyloid and tau. Clinical trials targeting amyloid and APP pathways in DS are underway, leveraging predictable disease progression to accelerate therapeutic development. Studying AD in DS provides a unique lens into the natural history of Alzheimer's disease, offering critical insights into genetic drivers, biomarker evolution, and therapeutic opportunities. The genetically defined and biologically concordant nature of DS-AD enables precise staging and early intervention strategies that can be translated to sporadic and familial AD. Continued investment in DS research will advance biomarker validation, refine clinical trial design, and inform personalized treatment approaches for the broader AD population.

Individuals with Down syndrome (DS) are more susceptible to periodontal disease; however, microbial changes following treatment remain insufficiently understood. This study evaluated the effects of nonsurgical periodontal therapy on clinical outcomes and oral microbiome dynamics in 6 patients with DS using 16S rRNA gene amplicon sequencing. Bacterial diversity, composition, network structure, and predicted functional pathways were analyzed using dental plaque samples. Bleeding on probing decreased significantly (p=0.047) after treatment, with a trend toward reduction in periodontal inflamed surface area (p=0.05). The abundance of Fusobacteria at the class level decreased significantly after treatment. The abundance of Mogibacterium timidum was higher in the pretreatment group than in the posttreatment group. M. timidum was positively correlated with Treponema denticola and associated with multiple bacterial taxa in the network during pretreatment. Predicted functional pathways related to aromatic compound degradation were more abundant in posttreatment samples than in pretreatment samples. An increase in the abundance of Fusobacterium and the positive correlation between T. denticola and M. timidum, together with their associations with other periodontal pathogens before treatment, may contribute to the development of periodontitis in individuals with DS. Nonsurgical periodontal therapy produces measurable clinical improvement and promotes microbial shifts in patients with DS.

This study evaluates plasma-based proteomic profiles for predicting amyloid positivity in adults with Down syndrome (DS) and examines the impact of apolipoprotein E ε4 (APOE ε4) on test performance. Cross-sectional data from 290 adults with DS were analyzed using single molecule array (SIMOA) technology to measure plasma amyloid beta (Aβ)42, Aβ40, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau phosphorylated at threonine 181, and total tau. Amyloid burden was quantified using Pittsburgh Compound Band (18)F-florbetapir Aβ positron emission tomography. Support vector machine analyses were conducted with biomarkers as predictors and age, sex, and APOE ε4 carrier status as covariates. Age, GFAP, and NfL contributed the most to the model performance. The proteomic profile achieved an area under the curve (AUC) of 96% in models with and without APOE ε4. These findings suggest that plasma proteomic biomarkers can effectively identify amyloid positivity in adults with DS and may support clinical triage, monitoring, and selection for clinical trials, independent of APOE ε4 status.

Establishment and characterization of induced pluripotent stem cell lines from individuals with Down syndrome and age-matched euploid donors.

Congenital duodenal obstruction (CDO) is a recognised anomaly frequently associated with Down syndrome (DS). While complete obstruction is typically diagnosed in the neonatal period, incomplete obstruction may present with milder, non-specific symptoms, often delaying diagnosis.We report a boy in early adolescence with DS and autism spectrum disorder (ASD) in whom CDO was diagnosed in adolescence. Since early childhood, his eating behaviour was restricted to finely chopped foods, initially interpreted as a behavioural feature related to DS and ASD. This likely masked gastrointestinal symptoms and contributed to the delayed recognition of CDO. It is also possible that subclinical duodenal obstruction became symptomatic as food intake increased during puberty.This case highlights the importance of considering incomplete CDO in children with DS, especially those with ASD, when persistent feeding difficulties are present-particularly if attributed solely to developmental or sensory issues.

Community-acquired pneumonia (CAP) is a frequent cause of morbidity in individuals with Down syndrome (DS) due to their inherent immunological vulnerabilities and anatomical predispositions. We present the case of a young woman in late adolescence with DS who developed severe CAP with radiological findings mimicking pulmonary tuberculosis. Despite initial diagnostic uncertainty, the patient improved remarkably following initiation of antibiotics combined with injectable corticosteroids. This case highlights both the diagnostic challenge of distinguishing CAP from tuberculosis in high-risk populations and the therapeutic value of corticosteroids as an adjunctive treatment in severe CAP.